Abstract
We hereby present the case of a 25-year-old man who presented at the emergency department of Civil Hospital Karachi, Pakistan with signs and symptoms of acute viral hepatitis. Serology tests revealed that the patient was suffering from hepatitis E viral (HEV) infection. Concurrently, the patient was also found to have thrombocytopaenia (TCP). His TCP became better after the resolution of his jaundice, with the patient requiring a transfusion of one mega unit of platelets. After ruling out other common causes of TCP and after a thorough literature search, we concluded that an immune-mediated mechanism secondary to HEV infection might have been the cause behind his low platelet counts. Hence, we propose considering the possibility of HEV infection in patients presenting with acute liver failure and TCP, irrespective of age, gender, and geographical location of the patient.
Introduction
Hepatitis E virus (HEV) is an RNA virus that is the only member of the genus Hepevirus in the family Hepeviridae. It causes viral hepatitis through oro-fecal contamination after an incubation period of 8–10 weeks. Clinical attack rates are highest among young adults. Asymptomatic and anicteric infections are also common. Chronic HEV infection is not observed. 1
Thrombocytopaenia (TCP) (platelet count <150 × 103/µL) is caused by a variety of factors that includes splenomegaly, bone marrow disorders, auto-immune diseases, pregnancy, drugs and so on. Hepatitis E infection has been associated with severe TCP through an immune-mediated mechanism.
Case report
A 25-year old man, with no known co-morbidities, came to the emergency department of our hospital with complaints of fever, vomiting, epigastric and right hypochondrial pain for the past 1 week.
The fever was sudden in onset, intermittent, initially low-grade, progressing to high-grade (101–103°F) with no rigors or chills and associated with generalised body ache, malaise, loss of appetite and two episodes of non-bilious vomiting. He was also complaining of epigastric and right hypochondrial pain, which was sudden in onset, continuous in nature and moderate in severity. On examination, the patient was icteric, with a soft abdomen and tenderness in the right hypochondrial region. The liver was enlarged three finger-breadths below the costal margin, and no splenomegaly was appreciated.
On admission, his liver function tests (LFTs) showed markedly raised serum glutamic-pyruvic transaminase (SGPT) of 1,045 U/L and total bilirubin of 11.93 mg/dL (direct bilirubin = 5.76 mg/dL; indirect bilirubin = 6.17 mg/dL). Alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), serum protein, prothrombin time (PT) and activated partial thromboplastin time (APTT) were all within normal limits. Complete blood count (CBC) showed isolated thrombocytopaenia with platelet count of 9 × 103/µL, while haemoglobin (Hb = 15.7g/dL) and total leukocyte count (TLC = 10.1 × 103/µL) were within normal range. Electrolytes, blood urea nitrogen (BUN), creatinine (Cr) and urine analysis were normal. Imaging studies showed normal chest X-ray, while abdominal ultrasound showed coarse echotexture of liver parenchyma. Bone marrow biopsy showed normocellular marrow with normal number of megakaryocytes.
Supportive therapy was initiated with intravenous fluids, vitamin K injection (I/M for 3 days) and transfusion of mega units of platelets. Oral anti-malarial drugs (Lumefantrine: 480 mg, Artemether: 80 mg) were started empirically.
However, blood smear was found to be negative for malarial parasite and serologic tests for dengue, anti-HAV IgM, hepatitis B and C, and HIV were all negative. Bone marrow biopsy showed normocellular marrow with a normal number of megakaryocytes. On the third day of admission, he was tested for anti-hepatitis E virus IgM antibodies, which were found to be positive (>4.0, cut-off rate: 0.466).
The patient was transfused with one mega unit of platelets. He responded to supportive therapy, and his platelet count rose gradually from 38 × 103/µL on the third day of admission to 90 × 103/µL on the seventh day of admission with improving LFTs.
The patient was kept hospitalised for another 5 days whereby his platelet count increased to 174 × 103/µL. The patient was discharged at a total bilirubin level of 4.72 mg/dL. Follow-up 1 week later showed complete resolution of jaundice.
Discussion
HEV is widely known to have been a source of mortality for pregnant women, with fatality rates as high as 20% reported in the second and third trimesters.2,3
Initially, it was believed that the virus has a limited geographical distribution. However, serological studies in absence of overt disease suggest that HEV may be endemic also in the United States and Europe, 4 as well as Asia and Africa.
There is no specific treatment available for HEV infection. A clean drinking water supply appears to be the best preventive strategy. 1
TCP alone or with other blood abnormalities can occur in infections including those caused by viral hepatitis and sometimes is the only presentation of viral hepatitis. Its mechanism is dependent upon the cause of infection and the severity of liver injury. 5
TCP’s occurrence in acute hepatitis A, B, C and E is usually never abrupt or severe and is similar to the TCP associated with varicella, rubella and mumps in children. Persistent TCP occurs with chronic hepatitis B and C infections. 5
In medical literature, TCP in association with hepatitis C and hepatitis B has been shown to have an auto-immune origin, with the affected patients having elevated titers of platelet-associated immunoglobulin G. 6 In chronic hepatitis C patients without splenomegaly, steroid therapy seemed to improve the degree of TCP, thereby indicating an immunological basis yet again. 7 A study by Hernández et al. revealed antiplatelet antibodies in 81% of hepatitis C patients with TCP. 7
This is, to the best of our knowledge, the fourth reported case of HEV infection being associated with TCP. Two of the previous three cases were of Indian men (aged 34 and 38 years)8,9 and the third was a 72-year-old French woman. 10
An immune-mediated mechanism was suggested in all three cases.
Bone marrow aspirates of the patients reported by Singh and Gangappa 9 and Colson et al. 10 showed a normo-cellular marrow, similar to our patient, explaining the possibility of immune-mediated destruction of platelets. As described in our patient, none of the three patients were reported to have had splenomegaly.
The HEV sequence of the reported French woman was classified as genotype 3f. Genotype information of the remaining patients could not be obtained. Ali et al. 8 and Singh and Ganappa 9 reported haematuria and purpura in their patients, a finding inconsistent with ours.
The French woman reported by Colson et al. 10 responded to supportive therapy, much like our patient (who was also transfused).
The patient was kept hospitalised for another 5 days whereby his platelet count increased further. The patient was discharged and his follow-up visit 1 week later revealed resolution of jaundice, with normal platelet levels.
In summary, the case presented here shows the importance of considering HEV infection in differential diagnosis of any patient presenting with symptoms of acute hepatitis and severe TCP irrespective of age, gender and geographical distribution of the patient.
Footnotes
Declaration of conflicting interests
None declared.
Funding
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.